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WEARABLE BIO SENSOR
Seminar Report
Submitted in partial fulfilment for the award of degree of
Bachelor of Technology
In
Electronics & Communication Engineering
Submitted by: Guided by:
Department of Electronics Engineering
Rajasthan Technical University, Kota
May 2020
NAME: - PRITAM
CRN:- 16/373
Dr. Deepak Bhatia
Associate Professor
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CERTIFICATE
This is to certify that Seminar Report entitled “WEARABLE BIO SENSOR” which is submitted
by PRITAM in partial fulfillment of the requirement for the award of degree B. Tech. in
Department of Electronics & Communication, RAJASTHAN TECHNICAL UNIVERSITY,
KOTA is a record of the candidate own work carried out by her under my supervision. The matter
embodied in this thesis is original and has not been submitted for the award of any other degree.
Date: Supervisor
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DECLARATION
I hereby declare that this submission is my own work and that, to the best of my knowledge and
belief, it contains no material previously published or written by another person nor material which
to a substantial extent has been accepted for the award of any other degree or diploma of the
university or other institute of higher learning, except where due acknowledgment has been made
in the text.
Signature:
Name – PRITAM
Roll No. –16EUCEC036
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ACKNOWLEDGEMENT
It gives us a great sense of pleasure to present the report of the B. Tech seminar undertaken during
B. Tech. Final Year. I owe special debt of gratitude to Dr. DEEPAK BHATIA , Department of
Electronics & Communication, RAJASTHAN TECHNICAL UNIVERSITY,KOTA for his
constant support and guidance throughout the course of my work. His sincerity, thoroughness and
perseverance have been a constant source of inspiration for me. It is only his cognizant efforts that
my endeavors have seen light of the day.
I also take the opportunity to acknowledge the contribution of Dr. Dr. Jankiballabh Sharma,
Department of Electronics & Communication, RAJASTHAN TECHNICAL UNIVERSITY,
KOTA, for his full support and assistance.
I also would not like to miss the opportunity to acknowledge the contribution of all faculty
members of the department for their kind assistance and cooperation during the development of
my project. Last but not the least, i acknowledge my friends for their contribution in the completion
of the project.
Signature:
Name : PRITAM
Roll No.:16EUCEC036
Date : 03-05-2020
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INDEX
S.R.NO. TABLE OF CONTENT PAGE NO
I. COVER PAGE 01
II. CERTIFICATE 02
III. DECLARATION 03
IV. ACKNOWLEADGEMENT 04
V. INDEX 05
VI. TABLE OF FIGURE 06
VII. ABSTRACT 07
1. INTRODUCTION 08
2. - CLASSFICATION OF WEARABLE BIOSENSOR 12
2.1 RING SENSOR 12
2.2 SMART SHIRT (WEARABLE MOTHERBOARD) 17
2.3 WEARABLE SWEAT BIO SENSOR 26
2.4 TATTO SENSOR 34
2.5 CONATCT LENS SENSOR 36
2.6 THICK FILM TEXTILE SENSOR 37
2.7 MOUTH GUARD BIO SENSOR 38
2.8 WRIST WATCH 39
2.9 WRIST/HAND BAND SENSOR 40
2.10 GFC GLUCOSE SENSOR 41
2.11 PACKAGE LATCATE CHIP SENSOR 42
3. CONCLUSION 43
4. FUTURE TRENDS 44
5. REFERANCES 46
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TABLE OF FIGURE
FIG.NO. TABLE OF FIGURE PAGE NO
1 Systematic representation of function of bio sensor 8
2 Health monitoring system based on wearable bio sensor 10
3 Noise cancellation mechanism 13
4 Prototype of Ring Sensor 13
5 Block diagram of Ring Sensor 14
6 Smart shirt 17
7 Requirements of Smart Shirts 18
8 Architecture of Smart Shirt 20
9 Applications of Smart Shirt 23
10 Wearable sweat biosensors which continuously measure a variety of sweat compositions for
Health monitoring.
26
11 Sweat bio sensing platforms 27
12 The categories of wearable chemical sensors. 28
13 Fully integrated sensor arrays (FISA) for multiplexed perspiration analysis 28
14 System level characterizations and compensation 29
15 On-body real-time multiplexed monitoring 30
16 Wearable sensors for Ca2+ and ph monitoring of body fluids 31
17 Flexible micro sensor arrays for multiplexed heavy metals analysis. 32
18 Transdermal alcohol sensor 32
19 One-day monitoring of sweat glucose concentrations using wearable diabetes patch and
Blood glucose levels using commercial blood glucose meter
33
20 Hydration status analysis during group outdoor running using the wearable sensors. 33
21 Tattoo-based transdermal alcohol sensor 34
22 Schematic procedure to fabricate tattoo seal biosensor. 35
23 A schematic of the contact lens sensor 36
24 Screen –printed carbon electrodes on the underwear 37
25 Mouth guard biosensor with fully integrated wireless instrumentation electronics to
Continuous and real time electrochemical monitoring. Adapted
38
26 Mouth guard biosensor for lactate monitoring. 38
27 Glucowatch for continuous glucose monitoring 39
28 Wrist and head band biosensors 40
29 Working principle of GCF biosensor for glucose monitoring with calibration curves 41
30 Packaged lactate chip sensor 42
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ABSTRACT
Recent advancements in miniature devices have fostered a dramatic growth of interest of wearable
technology. Wearable Bio-Sensors (WBS) will permit continuous cardiovascular (CV) monitoring in a
number of novel settings. WBS could play an important role in the wireless surveillance of people during
hazardous operations (military, firefighting, etc.)or such sensorscould be dispensed during a masscivilian
casualty occurrence. They typically rely on wireless, miniature sensors enclosed in ring or a shirt. They
take advantage of handheld units to temporarily store physiological data and then periodically upload that
data to a database server via wireless LAN or a cradle that allow Internet connection and used for clinical
diagnosis.
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Chapter:1 INTRODUCTION
Wearable sensors and systems have evolved to the point that they can be considered ready for clinical
application. The use of wearable monitoring devices that allow continuous or intermittent monitoring of
physiological signals is critical for the advancement of both the diagnosis as well as treatment of diseases.
Wearable biosensors offer an endless range of potential ways to provide terms of timely diagnoses and to
monitor the efficacyof treatments.Being able to trackpersonal health metrics, measuring and maintaining
patients’ drug levels with great accuracy,maintain accurate measurements, as well as monitor potential
threats in patients’ external environments are a few of the many benefits of wearable biosensors.
Measuring, maintaining are just a few of the m a n y uses biosensors have, some of these applications,
particularly those intended for the sports industry, are likely to be available in medium term, which is
about three to five yearswhile, and will be made available long-term, which is above five year
A biosensor is a machine that consists of a bio receptor and a transducer and is used for transforming a
biological response into an electrical signal. The biosensor machine empowers one to measure the target
analytic by not using the reagents and also to decide the concentration of substances,this machine is also
used in the monitoring of the glucose in diabetes patients, detects the pesticides and also the contaminants
of the river water,it also detects the poisonous metabolites. The continuous measurement of raw materials
and products plays a vital role in the control of a biochemical process.
Wearable systems are totally non-obtrusive devices that allow physicians to overcome the limitations of
ambulatory technology and provide a response to the need for monitoring individuals over weeks or
months. They typically rely on wireless miniature sensors enclosed in patches or bandages or in items that
can be worn, such as ring or shirt. The data sets recorded using these systems are then processed to detect
events predictive of possible worsening of the patient’s clinical situations or they are explored to access
the impact of clinical interventions.
Biosensors are chemical sensors in which the analyte recognition is sensed through biochemical or
biological mechanisms. The interactions between the analyte and the sensing elements determine the
biological responses. In these interactions, some physical and chemical properties of the sensing elements
may vary depending on the analyte concentration. To assess these property changes,the sensor convert the
interaction responses into measurable physical quantities. This process of analyte recognition can then be
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achieved through various methods, such asrecognition by ions, nucleic acids, enzymes,and/or by cells and
tissues. Specifically, bio receptors are highly selective towards the analyte.
Fig. 1 Systematic representation of function of bio sensor
According to Transparency Market Research,the market potential for wearable biosensors is high, and
projected to reach a market value of $21.6 billion by 2020. It is projected that “The biosensors market is
expected to witness considerable growth owing to its wide array of applications in diabetes monitoring,
cardiac monitoring, drug discovery, agriculture, environmental and bio-defense practices”. The growth of
this market has been aided by the rise in the diabetic population coupled with an increase in the increased
demand for home-care and point-of-care diagnostics. Innovation reduced not only the size of biosensors
but reduced the pain experienced by the user as well. Primarily, the method of collecting input from the
user was to prick the user to obtain a droplet of blood. To eliminate the pain of a prick but still be able to
collect data, researchers came to the solution to use different media for analysis such as Interstitial Fluid
(ISF), sweat, tears, saliva, and many other types of media.
The use of wearable biosensors is always beneficial as they provide continuous monitoring. They are easy
to use and their use reduces the hospitalization fee. Wearable biosensors are not only responsible for the
measurement of a biomarker, but also sends the signals through the advanced wireless systems to the
control unit. Emergency situations are detected via data processing implemented throughout the system
and an alarm message is sent to an emergencyservice center to provide immediate assistance to patients.
This creates a two-way feedback between doctors and patients allowing patients to get advice from their
doctors without physically going to the hospital. Utilizing the information provided by wearable
biosensors, patients have the potential to shorten hospital staysand reduce readmissions by being informed
about their health. A conceptual representation of a system for remote monitoring is shown in Fig 2.
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Fig. 2 Health monitoring system based on wearable bio sensor
1.1History of Wearable Biosensors:
In the year of 1956, Professor Lenald C Clack proclaimed a paper about oxygen electrode and later in the
year of 1962, the Professor came with an advanced idea that includes the enzyme transducers as the
membrane enclosed sandwiches. After this many people did many developments in it and then in the year
of 1976, La Roche introduced the Lactate Analyzer LA640. In 1987, for home blood glucose monitoring a
pen sized meter was launched and then in the year of 1996, the sales of this meter reached 175 million
dollars.
1.2Applications of the Wearable Biosensors:
The applications of the wearable biosensors are as follows:
 The biosensors are used in medical care for both the clinical purpose and the laboratory purpose.
 The biosensors are used in the resolution of food quality.
 It is used in detecting the pollutants of an environment.
 The biosensors are used in the industrial process control.
 In the process control, it will be able to measure the materials in the process flow of temperature,
acidity regulations and the pressure.
 The advancement of the biosensors in the industries can develop the manufacturing mechanisms.
 It plays a vital role in the production of pharmaceuticals.
 The biosensors are also used in the replacement of organs like an artificial pancreas for the
diabetic patient.
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1.3Needfor Biosensors:
The need for the biosensors is in the following areas:
 In the diagnostic market
 In the clinical testing
 In other materials that include veterinary and agricultural applications
 In specificity, it is used to measure particular analytes
 In the speed
 Simplicity and continuous monitoring capability
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Chapter:2 CLASSIFICATION OF WEARABLE
BIO SENSOR
2.1 RING SENSOR
It is a pulse oximetry sensor that allows one to continuously monitor heart rate and oxygen
saturation in a totally unobtrusive way. The device is shaped like a ring and thus it can be worn for
long periods of time without any discomfort to the subject. The ring sensor is equipped with a low
power transceiver that accomplishes bi-directional communication with a base station, and to upload
date at any point in time.
2.1.1 BASIC PRINCIPLE OF RING SENSOR:-
Each time the heart muscle contracts, blood is ejected from the ventricles and a pulse of pressure is
transmitted through the circulatory system.
This pressure pulse when traveling through the vessels, causes vessel wall displacement which is
measurable at various points.inorder to detectpulsatile blood volume changesby photoelectric method,
photo conductors are used. Normally photo resistors are used, for amplification purpose photo
transistors are used.
Light is emitted by LED and transmitted through the artery and the resistance of photo resistor is
determined by the amount of light reaching it.with each contraction of heart, blood is forced to the
extremities and the amount of blood in the finger increases.it alters the optical density with the result
that the light transmission through the finger reduces and the resistance of the photo resistor increases
accordingly. The photoresist or is connected as a part of voltage divider circuit and produces a voltage
that varies with the amount of blood in the finger. This voltage that closely follows the pressure pulse
2.1.2 WORKING
The LEDs and PD are placed on the flanks of the finger either reflective or transmittal type can be
used. For avoiding motion disturbances quite stable transmittal method is used. Transmittal type has a
powerful LED for transmitting light across the finger. This power consumption problem can be solved
with a light modulation technique using high-speed devices. Instead of lighting the skiing
continuously, the LED is turned ON only for a short time, say 10-100 ns, and the signal is sampled
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within this period, high frequency, low duty rate modulation is used for preventing skin-burning
problem.
The motion of the finger can be measure with an optical sensor. This motion detector can be used
not only for monitoring the presence of motion but also for cancelling the noise. By using PD-B as a
noise reference,a noise cancellation filter can be built to eliminate the noise of PD-A which completes
with the noise references used. And adaptive noise cancellation method is used.
Fig. 3 Noise Cancellation Mechanism
The noise-canceling filter combines two sensor signals; one is the main signal captured by PD-A and
the other is the noise reference obtained by PD-B. The main signal mostly consists of the truce pulsate
signal, but it does contain some noise. If we know the proportion of noise contained in the main signal,
we can sensate the contained in the main signal, we can generate the noise of the same magnitude by
attending the noise reference signaland then subtract the noise from the main signal to recover the true
pulsatile signal.
Fig. 4 Prototype of Ring Sensor
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The ring has a microcomputer performing all the device controls and low level signal processing
including LED modulation, data acquisition, filtering, and bi-directional RF communication. The
acquired waveformssampled at100Hz are transmitted to a cellular phone carriedby the patient through
an RF link of 105Kbps at a carrier frequency of 915 MHz The cellular phone accesses a website for
data storage and clinical diagnosis.
2.1.3 BLOCK DIAGRAM OF RING SENSOR
Fig. 5 Block diagram of Ring Sensor
Power for light source, photo detector, RF transmitter and analog and digital processing units provided
by a tiny cell battery used for wrist watches. Lifetime is 2 or 3 weeks.
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Light Source: - Light source for the ring sensor is the LED, approximately wavelength of 660 nm.
Photo Detector: - Photo detector is normally photodiode or phototransistor used for detecting the
signal from the LED.
RF Transmitter: - It is used for transmitting the measured signals. Its carrier frequency is 915MHz.
LED Modulation
Power consumption problem can be solved with a lighting modulation technique. Instead of lighting the
skin continually the LED is turned on only for a short time, say 100-1000ns and the signal is sampled
within the period. High frequency low duty cycle modulation implemented minimizes LED power
consumption.
Data Acquisition:-It is used to collect the data from sensor and data are sampled and recorded.
Filtering
The signal from the PD-Basa noise reference a noise cancellation filter canbe built to eliminate the noise
of PD-Awhich correlateswith the noise reference signal. For noise cancellation we use the adaptive noise
filter.
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2.1.4 APPLICATION OF THE RING SENSOR
 CATRASTOPHE DETECTION
 Wireless supervision of people during hazardous operations
Ex: military, fire fighting
 In an overcrowded emergency department
 CHRONIC MEDICAL CONDITION
 in cardiovascular disease for monitoring the hyper tension
 chronic surveillance of abnormal heart failure
2.1.5 ADVANTAGE
 continuous monitoring
 detection of transient phenomena
 promote further diagnostic and therapeutic measures
 easy to use
 reducing hospitalization fee
2.1.6 DISADVANTAGE
 initial cost is high
 limited number of physiological parameters are to be monitored
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2.2 SMART SHIRT (WEARABLE MOTHERBOARD)
Smart shirt developed at Georgia tech which represents the first attempt at relying an unobtrusive,
mobile and easy to use vital signs monitoring system; presents the key applications of the smart shirt
technology along with its impact on the practice of medicine; and covers key opportunities to create
the next generation of truly “adaptive and responsive” medical systems.
Research on the design and development of a smart shirt fort a combat casualty care has led to the
realization of the world’s first wearable motherboard or an “intelligent” garment for the 21st
century.
The Georgia tech wearable motherboard (GTWM) uses optical fibers to detect bullet wounds and
special sensors and interconnects to monitor the body vital signs during combat conditions. This
GTWM (smart shirt) provides an extremely versatile framework for the incorporation of sensing,
monitoring and information processing devices. The principal advantage of smart shirt is that it
provides for the first time a very systematic way of monitoring the vital signs of humans in an
unobtrusive manner
Fig. 6 SMART SHIRT
2.2.1REQUIREMENTS OF SMART SHIRT
Casualties are associated with combat and sometimes are inevitable. Since medical resources are
limited in a combat scenario, there is critical need to make optimum use of the available resources to
minimize the loss of human life, which has value that is priceless. In a significant departure from the
past, the loss of even a single soldier in a war can alter the nation’s engagement strategy making it all
the important to save lives.
Similarly on the civilian side, the population is aging and the cost of the health care delivery is
expected to increase at a rate faster than it is today. With the decreasing number of doctors in rural
areas,the doctor/patient ratio is in certain instances reaching unacceptable levels for ensuring a basic
sense of security when they leave the hospital because they feel “cutoff” from the continuous watch
and care they received in the hospital. This degree of uncertainty can greatly influence their
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postoperative recovery.Therefore there is a need to continuously monitor such patients and give them
the added peace of mind so that the positive psychological impact will speed up the recovery process.
Mentally ill patients need to be monitored on a regular basis to gain a better understanding of the
relationship between their vital signs and their behavioral patterns so that their treatments can be
suitably modified. Such medical monitoring of individuals is critical for the successful practice of
telemedicine that is becoming economically viable in the context of advancements in computing and
telecommunication, likewise continuous monitoring of astronautsin space,of athletes during practice
sessions and in competition, of law enforcement personnel and combat soldiers in the line of duty are
all extremely important.
Fig. 7 Requirements of Smart Shirts
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2.2.2ARCHITECTURE
The GTWM was woven into a single –piece garment (an undershirt) on a weaving machine to fit a 38-40”
chest. The plastic optical fiber (POF) is spirally integrated into the structure during the fabric production
process without any discontinuities at the armhole or the segms using a novel modification in the weaving
process.
An interconnection technology was developed to transmit information from (and to) sensors mounted at
any location on the body thus creating a flexible “bus” structure. T-connectors –similar to “button clips”
used in clothing are attached to the fibers that serve as a data bus to carry the information from the sensors
(eg: ECG sensors) on the body.
The sensorswill plug into these connectors and atthe other end similar T-connector will be used to transmit
their information for monitoring equipment or DARPS (Defense Advanced Research Projects Agency)
personnel status monitor .By making the sensors detachable from the garments, the versatility Iof the
Georgia Tech Smart Shirt has been significantly enhanced. Since shapes and sizes of humans will be
different, sensors can be positioned on the right locations for all users and without any constraints being
imposed by the smart shirt can be truly “customized”. Moreover the smart shirt can be laundered without
any damage to the sensors themselves.
The interconnection technology hasbeen used to integrate sensorsfor monitoring the following vital signs:
temperature, heart rate and respiration rate .In addition a microphone has been attached to transmit the
weaver’s voice data to monitoring locations. Other sensors can be easily integrated into the structure. The
flexible data bus integrated into the stricture transmits the information from the suite of the sensors to the
multifunction processor known as the Smart shirt controller. This controller in turn processes the signals
and transmit them wirelessly to desired locations (eg: doctor’s office, hospital, and battlefield). The bus
also serves to transmit information to the sensors (and hence the weaver) from the external sources, thus
making the smart shirt a valuable information infrastructure.
A combat soldier sensor to his body, pulls the smart shirt on, and attaches the sensors to the smart shirt.
The smart shirt functions like a mo0therboard, with plastic optical fibers and other special fibers woven
throughout the actual fabric of the shirt. To pinpoint the exact location of a bullet penetration, a “signal” is
sent from one end of the plastic optical fiber to a receiver at the other end. The emitter and the receiver are
connected to a Personal Status Monitor (psm) worn at the hip level by the soldier. If the light from the
emitter does not reach the receiver inside the PSM,it signifies that the smart shirt has been penetrated (i.e.;
the soldier has been shot). The signal bounces back to the PSM forum the point of penetration, helping the
medical personnel pinpoint the exact location the solider wounds.
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The soldiers vital signs –heart rate, temperature, respiration rate etc. are monitored in two ways: through
the sensors integrated into the T-shirt: and through the sensors on the soldier’s body, both of which are
connected to the PSM. Information on the soldiers wound and the condition is immediately transmitted
electronically from the PSM to a medical triage unit somewhere near the battlefield. The triage unit them
dispatches the approximate medical personnel to the scene .The Georgia tech smart shirt can help a
physician determine the extent of a soldiers injuries based on the strength of his heart beat and respiratory
rate. This information is vital for accessing who needs assistance first during the so-called “Golden Hour”
in which there are numerous casualties.
Fig. 8 Architecture of Smart Shirt
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2.2.3APPLICATIONS OF SMART SHIRT
 Combat casualty care.
 Medical monitoring.
 Sports/ Performance monitoring.
 Space experiments.
 Mission critical/ hazardous application.
 Fire- fighting.
 Wearable mobile information infrastructure.
The vital signs information gathered by the various sensors on the body travels through the smart shirt
controller for processing, from these, the computed vital signals are wirelessly transmitted using the
“communication information infrastructure” in place in that application (e.g.: the firefighters,
communication systems, battlefield communication infrastructure, the hospital network) to the
monitoring station. There, the back-end Data display and Management system – with a built –in
knowledge –based decision support system- in reverse these vital signs ask in real-time and provide
the right response to the situation.
Table 1 summarizes the broad range of application of the smart shirt technology. The table also
shows the application type and the target population that can utilize the technology.
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Table No:- 1 Wearable smart shirt applications
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Fig. 9 Applications of Smart Shirt
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2.2.4IMPACT OF THE SMART SHIRT
The smart shirt will have significant impact on the practice of medium since it fulfills the critical
need for a technology that canenhance the quality of life while reducing the health care costacross
the continuum of life that is from newborns to senior citizens, and acrossthe continuum of medical
care that is from hospitals and everywhere in between.
The smart shirt can contribute to reduction in health care cost while enhancing the quality of life.
For instance, patients could wearthe smart shirt at home and be monitored by a monitoring station;
thereby avoiding hospital stay cost and reducing the overall cost of healthcare. At also same home,
a home setting can contribute to faster recovery. For example, if the patient recovering at home
from heart surgery is wearing the smart shirt, the ECG can be transmitted wirelessly (through
mobile phone, internet etc.) to the hospital on a regular basis. This monitoring will help the patient
feelmore “secure” and will facilitate the recuperation while simultaneously reducing the cost time
associated with recovery. Moreover, in the event of an emergency, the doctor can be notified
instantaneously. Using the online medical records (available over the web) the physician can
administrate the right investment at the right time at the right cost and indeed save a life, thereby
realizing the full potential of the smart shirt technology.
Furthermore, persons who have known disorders can wear the smart shirt and be under
constant monitoring of the physical conditions by medical personnel. Yet another potential impact
of the smart shirt technology is the eventual disappearance of geographical/physical boundaries as
barriers for individual seeking the best in healthcare worldwide.
The smart shirt technology has the means to provide unobstructed monitoring for
individuals and can thereby play a critical role disease management for the large numbers of
individuals at risk for high blood pressure, heart disease, diabetes, chronic bronchitis, and
depression by enabling early systematic intervention.
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2.2.5ADVANTAGES OF THE SMART SHIRT
 Continuous monitoring
 Right Treatment at the right time at the right cost
 Easy to wear and takeoff.
 Reducing the health care cost
2.2.6DISADVANTAGES OF THE SMART SHIRT
 Initial cost is high
 Battery life is less
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2.3WEARABLE SWEAT BIO SENSOR:-
Wearable biosensors are expected to play a significant role in future healthcare as they allow real-time and
non-invasive (or minimally invasive) monitoring of an individual’s health state. Currently commercialized
wearable sensors are only capable of tracking an individual’s physical activities and vital signs but fail to
provide insightful physiological information at the molecular level. Human sweat,an important body fluid
that can be retrieved conveniently and non-invasively, contains rich information about our health and
fitness conditions. Therefore,sweatcanbe an ideal candidate for developing wearable chemical biosensors
which may provide insightful physiological information. In the past decade,tremendous progress has been
made on developing such sweat biosensors as illustrated in Table No-2 These wearable biosensors have
been used to measure the detailed sweat profiles of a wide spectrum of analytes including metabolites,
electrolytes and heavy metals during various indoor and outdoor physical activities.
Fig. 10 Wearable sweat biosensors which continuously measure a variety ofsweat compositions for
health monitoring.
Platform Analytes Refs.
Temporary tattoo
Lactate, pH, NH4
+
, Na+
, Zn2+
, ethanol 7-12
pH 13
Patch
Glucose, lactate, Na+
, K+
, pH, Ca2+
, Zn2+
, Cu2+
4-6
Glucose, pH 14
Na+
15-17
Cl-
18, 19
pH 20, 21
Table No:- 2 Summary of the wearable sweat biosensor
.
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2.3.1 SYSTEM DESIGN OF WEARABLE BIO SENSOR:-
2.3.1.1 Platform of sweat biosensor:-
Wearable sweat biosensor are usually prepared on a flexible substrate that forms conformal contact with
the skin, while minimizing the required sweat volume to perform proper sweat collection and analysis.
Different sensing platforms have been developed in the past decade which include the epidermal tattoos,
flexible patches/bands and textiles.
Fig. 11 Sweat bio sensing platforms: a) epidermal temporary tattoo b) adhesive RFIDsensor patch
c) flexible and stretchable sensor patch d) fully integrated flexible sensor band.
2.3.1.2 Target of analytes
Avariety of sweatbiomarkers are closely relatedto human health conditions, andthey canserve asexcellent
targeting analytes for wearable sweat biosensors. For example, sweat chloride test is the gold standard for
diagnosis of cystic fibrosis; excessive loss of Na+
and K+
in sweat could result in hyponatremia,
hypokalemia, muscle cramps or dehydration; sweat ethanol and glucose are reported to be metabolically
related to blood ethanol and glucose; sweat lactate can potentially serve as a sensitive marker of pressure
ischemia. Monitoring these important biomarkers using wearable sweat biosensors can offer us insightful
physiological and clinical information.
2.3.1.3 Detection techniques:-
Based on detection strategies, current wearable sweat biosensors include optical sensors for sweat rate
and sweat pH analysis , impedance-based sensors for sweat conductivity and sweat rate monitoring, ion
selective electrodes for electrolyte sensing (such as Na+
,K+
, H+
, NH4
+
,Ca2+
, Cl-
), enzymatic
amperometric sensors for metabolite sensing (such as glucose, lactate,uric acid, ethanol), and stripping
based sensors for heavy metal analysis (such as Cu, Zn, Pb, Cd, Hg).
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Fig. 12 The categories of wearable chemical sensors.
2.3.1.4 System integration
Since sweat secretion is complex, to extract more useful information, simultaneous
detection of multiple sweatbiomarkers through system integration is critical. A fully integrated multiplexed
sweat sensing system has been developed by merging plastic-based sensors that interface with the skin and
silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. Figure 13
shows a schematic of the sweat sensor array consisting of 2 metabolite sensors (glucose and lactate), 2
electrolyte sensors (Na+
and K+
) and a skin temperature sensor. Figure 13 illustrates the system-level
overview of the signal transduction, processing, and wireless transmission paths to facilitate multiplexed
on body measurements. Eventually the data from the system is wirelessly transmitted to a cellphone and
displayed in a custom developed application.
Fig. 13 Fully integrated sensor arrays (FISA) for multiplexed perspiration analysis a) Schematic of
the sensor array (including glucose, lactate, sodium, potassium and temperature sensors). b)
System-level block diagram of the FISA.
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2.3.1.5 System level characterizations and compensation:-
It has been shown that each sensor can maintain excellent selectivity upon varying concentrations of each
analyte during system-level multiplexed measurements (Figure 14a). However, temperature and pH have
shown great influence on the performance of amperometric enzymatic based sensors (Figure14b and 14c).
Utilization of such fully integrated wearable device can facilitate measurement accuracy through real-time
calibration and signal compensation.
Fig. 14 . a) System-levelmultiplexedmeasurements andinterference studies. b)System-levelreal-
time temperature andpH (c) compensation for enzymatic sensors.
2.3.2 Real time on body sweat analysis for health monitoring
The sweat biosensors can be worn on body for real-time perspiration analysis during a variety of physical
activities, allowing non-invasive health monitoring. Recently, the on body evaluation of sweat biosensors
has opened the door for a wide range of physiological and clinical investigations.
2.3.2.1 Real time analysis of major sweat metabolites (glucose and lactate) and major
electrolytes (Na+ and K+)
Physiological monitoring of sweat lactate and sodium using wearable sweat sensors has been demonstrated
on different platforms. Simultaneous measurements of multiple sweat analytes using a fully-integrated
sensing system wasalso reported during a cycling. Figure 15 shows that, asperspiration begins, both lactate
and glucose levels in sweat decrease gradually. The decreased sweat lactate and glucose levels is owing to
the dilution effect caused by an increase in sweat rate, which is visually observed as exercise continues.
30 | P a g e
Sweat [Na+
] increases and [K+
] decreases in the beginning of perspiration, in line with the previous ex-situ
studies from the collected sweat samples. Both [Na+
] and [K+
] stabilize as cycling continues.
Fig. 15 On-body real-time multiplexed monitoring ofsweat glucose, lactate, sodium, potassium as
well as the skin temperature using a FISA worn on a subject’s forehead during a constant-load
cycling exercise
2.3.2.2 . Real time sweat Ca2+ and pH monitoring
Calcium is an essentialcomponent for human metabolism, and pH is crucial for potential disease diagnosis.
Sweat pH sensors have been measured optically and electrochemically. A fully integrated wearable sensing
device (Figure 16a) has also been demonstrated for simultaneous evaluation of pH and Ca2+
in human
perspiration which is particularly important considering that free Ca2+
level in bio fluids is dependent on
pH . Figure 16 b displays the sweat profiles of a subject during a constant load cycling exercise: sweat pH
increases gradually for 5 min and then stabilizes in the remaining cycling exercise while the Ca2+
sensor
shows an opposite trend. The responses of these sensors were validated with a commercial pH meter and
inductively coupled plasma-mass spectrometry.
31 | P a g e
Fig. 16 Wearable sensors for Ca2+ and pH monitoring of body fluids a) A schematic of a flexible
sensor array. b) On-body Ca2+ and pH analysis during a constant-load cycling exercise
2.3.2.3 Sweat heavy metal monitoring:-
Besides metabolites and electrolytes, a variety of heavy metals canbe found in human sweatand are closely
related to human health conditions. Printed tattoo based sweat sensors have been used for sweat Zn
monitoring. Recently, a micro sensor array containing biocompatible gold and bismuth electrodes has been
developed to simultaneously measure multiple heavy metals in sweat including Zn, Cd, Pb, Cu, and Hg
through stripping voltammetry (Figure 17a-c). Sweat Cu and Zn were monitored on-body during a cycling
exercise (Figure17d). These trace metals sensors can monitor heavy metal exposure and aid in related
clinical investigations.
32 | P a g e
Fig. 17 Flexible micro sensor arrays for multiplexed heavy metals analysis. a) Schematic of
microelectrodes. b, c) Characterization of Au and Bi microelectrodesfor trace metal detection.
d) On body trace metal detection during a constant-load cycling exercise.
2.3.2.4 Ethanol monitoring:-
High blood alcohol levels can cause severe traffic accidents and increased risks for cancers while sweat
ethanol is reported to be the same as blood alcohol concentration (BAC). Wearable sweat ethanol sensors
which integrate an iontophoresis based sweat extraction system along with a flexible wireless circuit board
have been developed. These sensors demonstrate clear differences in the current response before and after
alcohol consumption, reflecting the increase of blood ethanol levels (Figure 18).
Fig. 18 Transdermal alcohol sensor . a) Schematic diagram of the wireless operation of the iontophoretic -
sensing tattoo device for transdermal alcohol sensing. b) Experiments to demonstrate correlation between
BAC level and current response from the tattoo biosensor measured.
33 | P a g e
2.3.2.5 Glucose correlation study:-
The wearable sweat biosensors can potentially be used for diabetes monitoring and control. A graphene-
based electrochemical device has recently been developed to measure real-time sweat glucose through pH
calibration. With the aid of this device, a correlation betweensweatglucose data from the wearable diabetes
patch and those from a commercial glucose assay as wellas blood glucose data from a commercial glucose
meter was observed.fig-19)
Fig. 19 One-day monitoring ofsweat glucose concentrations using wearable diabetes patch and
blood glucose levels using commercial blood glucose meter
2.3.2.6 Dehydration monitoring:-
Monitoring hydration status is of the utmost importance to athletes because fluid deficit impairs endurance
performance. The sweat biosensors can be potentially used for effective and non-invasive monitoring of
the electrolyte loss (Figure 20a) Figure 20b shows that sweat [Na+
] measured from an integrated sensor
array was stable throughout running in dehydration trials (with regular water intake). On the other hand, a
substantial increase in sweat [Na+
] was observed in dehydration trials (without water intake) after 80 min
when subjects had lost a large amount of water (Figure 20c). The results show that through sweat
composition analysis, insightful information may be provided for athletic performance applications.
Fig. 20 Hydration status analysis during group outdoor running using the wearable sensors. a) Schematic illustration
showing the group outdoor running trial based on wearable FISAs (packaged as ‘smart headbands’). The data are
real-time transmittedto the user’s cellphone anduploadedto cloud servers. b) Representative real-time sweat sodium
levels during an endurance run with water intake (b) and an endurance run without water intake (c).
34 | P a g e
2.4 Tattoo sensor:-
Tattoo sensors are separated into two categories based upon the lifetime of the sensor: temporary and long
term. Temporary tattoo sensors are designed as disposable sensors with a maximum life time of 2-3 days.
Long term tattoo sensors are designed to uphold their functionality for an extended period. Here in depth
we will discuss under those categorize; temporary tattoos sensor, smart tattoos sensor.
2.4.1 Temporary tattoo sensor:-
Wearable temporary tattoos is capable of monitoring alcohol in a real-time and noninvasive way via the
integration of printed and flexible iontophoretic-sensing electrodes with wireless electronics. The flexible
tattoo-based iontophoretic alcohol monitoring patch uses transdermal delivery of a drug, pilocarpine to
induce sweat via constant-current iontophoresis. Followed by amperometric bio sensing of the sweat’s
ethanol (Fig. 21D). The latter relies on an alcohol-oxidase (AOx) enzymatic patch along with a printed
Prussian blue (PB) electrode transducer. A flexible supporting module with electronic readout was also
integrated for wireless data transmission (Fig. 21). The electrochemical performance of the alcohol
biosensor wasvalidated first in a medium bufferovera wide concentration range of 0–36 mM ethanol, which
corresponded to the physiological level of ethanol found in sweat. The enzymatic sensors are selective
towards ethanol and have very negligible interference with the co-existing compounds.
Fig. 21 Tattoo-based transdermal alcohol sensor. (A) Schematic diagram of an iontophoretic-
sensing tattoo device,containing the iontophoretic electrode.
35 | P a g e
2.4.2 Smart tattoo sensor:-
The pursuit ofa more accurate blood glucose level reading led to the invention of carbonnanotube
(CNT) ‘tattoos’. Most recently glucose sensors involve the injection of the enzyme, GOx which breaks
down glucose. These sensors have not meet the desired levelof stability and are only used for seven days of
use. What distinguishes smart tattoo sensor is the foundation of their use of its carbon nanotubes base. In
addition, these smart tattoo sensors can be immobilized in hydrogels that are highly biocompatible and
compatible with microfabrication.
The nanotube smart tattoo sensor would change fluorescence properties in response to blood
glucose, and this change could be read out using optical interrogation through the skin. This method would
eliminate or reduce the need for patients to take blood samples while allowing data to be collected in a more
continuous manner. Researchers usedthe nanoparticle inks in a saline solution that could be injected under
the skin like an actualtattoo and have found that the potential lifetime of up to six months for those tattoo.
Fig. 22 shows the CNT modified hydrogel based smart tattoo sensor. Glucose, lactate, and alcohol were
detected using the smart tattoos.
Fig. 22 Schematic procedure to fabricate tattoo seal biosensor. B. Schematic of detection mechanism. Each
dehydrogenase and diaphoresis are modified with CNT and hydrogel shells include tetrazolium for
optical detection of targets.
36 | P a g e
2.5 Contactlens sensors:-
In 2015, the Food and Drug Administration (FDA) approved Google’s patent for contact lenses
based sensors. These devices may help healthcare professionals to determine the optimal time of day for
measuring a patient’s intraocular pressure. Elevated levels of intraocular pressure associated optic nerve
indicates damage that is a characteristic of glaucoma. The contact lenses are able to measure glucose and
lactate concentrations. The contact lenses are constructed with a tear film which consists of three layers: an
outer lipid layer, aqueous layer, and the inner mucin layer. Fig.23 shows the pictures and configurations of
the contact lenses sensors. For these types of sensors, shelf life is limited due to the degradation of enzymes
that occurs because of high temperatures and exposure to light. The sensors are tested continuously for 24
hours, using 288 measurements. The stability can, however, be increased by encapsulating the enzyme. Jin
Zhang from a Chemical and Biochemical Engineering department, University of Western Ontario,
developed the technology which uses engineered nanoparticles embedded into hydrogel lenses. The
nanoparticles are engineered to react with the glucose molecules contained in tears. When sugar levels
changes, a chemical reaction causes the lens to change color, allowing the wearer to adjust their glucose
accordingly.
Fig. 23 Aschematic ofthe contact lenssensor, showing the electrical circuitry ofthe sensing system.
(b) The contact lens sensor prototype. (c) The wireless chip, which is mounted with the sensor,
onto an electronic ring, and then embedded into the contact lens
37 | P a g e
2.6Thick Film textile based sensor:
The textile based printed carbon electrodes usually have smooth conductor edges with no defects
and cracks. The Screen printed carbon electrodes on the underwear and its voltammetry scan has been
shown as Fig.24. The favorable electrochemical behavior is maintained under fold in or stretching stress.
It is amperometric sensor which measures NADH and H2O2 from the body by using dehydrogenase oxide
basedenzyme with partial voltammetry method. This is undergarment biosensor which remains stable upon
successive stretching. Direct screen printing underwear based carbon electrode is used for the operation.
Future applications would definitely gain the advantages from tailoring the ink composition and printing
conditions as per the customer requirements.
Fig. 24 Screen –printed carbon electrodes on the underwear along with the morphology of a single
electrode and linear scan voltammetry response for increasing NADH concentrations over the 0-
100 uM range.
38 | P a g e
2.7 Mouth guard bio sensor:-
A concept of mouth guard metabolite biosensor has been reported by Kim et al. This is an
amperometric biosensor with salivary lactate as an analyte. The direct measurement of lactate in saliva
would be used as a diagnostic tool for in vitro monitoring as salivary lactate concentration corresponds with
the blood lactate concentration. This wearable oral bio-sensory system uses LOx as an enzyme with
Prussian –Blue modified electrode as transducer, acting as artificial peroxidase to offer selective detection
of the H2O2. With the aim of stabilizing the device, LOx wasimmobilized on the working electrode surface
by the method of polymer entrapping. It parades high selectivity, sensitivity and stability, so as to use them
in getting information regarding wearer’shealth,performance and stresslevelthrough Bluetooth orwireless
network as displayed in Fig.25.
Fig. 25 Mouth guard biosensor with fully integrated wireless instrumentation electronics to
continuous and real time electrochemical monitoring. Adapted
With the intention of analyzing the stability of the sensor, the researchers have taken continuous readings
over the interval of 10 minutes for 2 hours and it has been noticed that the sensor displays high stability
with small variations of current signal, ranging between 90% and 106% of the actual response. The good
stability shows the proactive actions of the Poly- orthophenylenediamine–LOx interaction, where it is used
to stabilize the device. The continuous monitoring responses are known in the Fig.26 below:
Fig. 26 Mouth guard biosensor for lactate monitoring.
39 | P a g e
2.8 Wrist watch (gluco watch )
GlucoWatch or GlucoWatch biographer is a wrist watch potentiostat [Fig. 27]. It has GOx enzyme
and uses ISF to measure glucose level. This Amperometric sensor works on reverse Iontophoresis
phenomenon. The readings have been taken continuously for 12-13 hours with the frequency of 3 per hour.
This sensor facilitates with the memory to save up to 4000 readings. It gives 78 readings per wear. After
that, one has to change the sensor or stabilize the enzyme in order to continue the use. Gluco watch G2
biographer is suitable for adults and gained FDA approval for use in children and adolescents to monitor
glucose continuously. Patients who are insulin dependent are required to monitor their blood glucose levels
to ensure that appropriate levels of insulin are circulating.
Fig. 27 GlucoWatch for continuous glucose monitoring
40 | P a g e
2.9 Wrist/hand band bio sensor:-
A mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for
multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites
(such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin
temperature (to calibrate the response of the sensors). These kinds of biosensors are majorly found in
athlete’s group for continuous health monitoring while exercising [Fig.28]. The device come in the form of
Wrist or head band with a credit card sized amperometric biosensor embedded in it. It uses GOx and LOx
enzyme which monitors glucose contents present in the sweat.
Fig. 28 Wrist and head band biosensors
41 | P a g e
2.10 GFC GLUCOSE SENSOR :-
To monitor blood glucose level, one method has been used where to realize a non-invasive blood glucose
monitor, the Gingival Crevicular Fluid (GCF) wasmeasured.The device to collect GCF wasdeveloped that
was designed to be disposal, biocompatible and small enough to be inserted in the gingival crevice for
collection of micro liters sample of GCF. Fig. 29 shows working principle of GCF biosensor device and its
calibration curves for Capillary Blood Glucose (CBG) and GCF . It senses glucose with the help of GOx
enzyme. They monitored continuous responses with increased sensitivity, accuracy, repeatability and
specificity. The electrode used is ferrocene modified gold film electrode. Enzyme immobilization was done
with cross-linking method. It is a saliva based noninvasive glucose monitoring tool which is widely used
for clinical diagnostics. As the repeatability and ultimately stability is higher, it is used in diabetes
instantaneous glucose monitoring.
Fig. 29 Working principle of GCF biosensor for glucose monitoring with calibration curves
42 | P a g e
2.11 PACKAGED LACTATE CHIP SENSOR:-
The electrochemical and biological interferences from saliva were discriminated by using a dual platinum
electrode, common Ag/AgClreference electrode and blocking membranes. This is saliva based noninvasive
biosensor which monitors lactate level in saliva. It has high operational stability and long term continuous
salivary lactate monitoring is possible. The technique of enzyme probe electrode-analyte amperometric
monitoring has beenusedin this type of sensor.The structure of packageslactate chip sensors canbe studied
through Fig. 30. The reference electrode, counter electrode and cavity of working electrode has been
packaged with sealing foil and pores. One of the three salivary glands, sublingual (SL) measurement with
Lactate Oxide enzymatic detection has been conducted continuously with high stability.
Fig. 30 . Packaged Lactate Chip Sensor
43 | P a g e
CHAPTER:3 CONCLUSION
The development in wearable biosensors is best example of the integration of biological and engineering
sciences. It includes the research of biochemical field and understanding the interaction between biological
elements with the target molecule. The use of Nano-transducers has been increased in separation between
transducers and bio receptors. The immobilization and stabilization strategies can be selected based on the
application. For instance, while developing a sensorwhere durability is not an issue, (e.g.Temporary Tattoo
sensors) conventional methods of enzyme stabilization like of enzyme immobilization, cross-linking can
be used. For long- term sensing applications immobilization/stabilization using enzyme cloning, sol-gel
techniques, hydrogel/Nano gel incorporation would be a viable option. Investigating artificial receptor
system that mimic the enzymatic sensing pathway is another viable approach to design biosensor for long-
term stability.
44 | P a g e
Chapter:4 FUTURE TRENDS
Considering future demands of biosensors, researchers are heading towards the best possible solutions to
improve the methods of stabilization and achieve the most viable wearable biosensor. In order to maintain
the catalytic activity of enzyme in sensors,the sample environment is also a crucial factor to be considered.
The previous stabilization strategies have failed because of the diffusion of key reactants and products in
and out of the enzyme or matrix surface. For oxidase based enzymes, the coproduced hydrogen peroxide
might degrade the enzyme structures. Therefore, to improve the stability of GOx, some new techniques
have been proposed which including cross linking, silica sol-gel encapsulation, and molecular cloning.
However, these techniques also have some limitations. For examples, sol-gel encapsulation involves
production of some harmful organic solvents as byproducts. These are capable of destabilization of
encapsulated enzymes. This leads to the decrease in catalytic activity, decrease in substrate specificity and
increase enzyme inhibition. The factors which are capable to create an optimum environment for entrapped
GOx stability are given by. Molecular cloning is proposed to increase the intrinsic molecular stability [20].
It helps to maintain thermal resistance and pH stability of enzymes. Near future technique to improve the
stability is modification of enzymes’ molecular structures. The modification of enzyme structure as per the
requirements is most promising and versatile method to gain the stability without affecting performance of
biosensors. Another aspect to improve the stability is to incorporate enzymes on a hydrogel or Nano gel
matrix. These nanogels creates protecting layers by encapsulating the bio receptors, controls diffusion
process and enhances biocompatibility
.
By providing the “platform” for a suite of sensors that can be utilized to monitor an individual
unobtrusively. Smart Shirt technology opens up existing opportunities to develop “adaptive and
responsive” systems that can “think” and “act” based on the users condition, stimuli and environment.
Thus, the rich vital signs delta steam from the smart shirt can be used to design and experiment “real-time”
feedback mechanism (as part of the smart shirt system) to embrace the quality of care for this individual
by providing appropriate and timely medical inspections.
Certain individuals are susceptible to anaphylaxis reaction (an allergic reaction) when stung by a
bee or spider and need a shot of epinephrine (adrenaline) immediately to prevent above illness or even
fatalities. By applying advancement in MEMS (Micro-Electromechanical Systems)technology, a feedback
system including a dry delivery system-can be integrated into the smart shirt. Of course mechanism to
45 | P a g e
guard against inadvertent administration of dry can be built as a part of the control system.
Likewise, the Smart shirt’s delta acquisition capabilities can be used to detect the condition when
an individual is lapsing into a diabetic shock and this integrated feedback mechanism can provide the
appropriate response to prevent a fatality. Thus, the smart shirt represents yet another significant milestone
in the endeavor to save and enhance the quality of human life through the use of advanced technologies.
46 | P a g e
Chapter:5 REFERENCES
[1] A. Sonawane, P. Manickam, and S. Bhansali, “Stability of Enzymatic Biosensors for Wearable
Applications,” IEEE Rev. Biomed. Eng., vol. 10, pp. 174–186, 2017.
[2] Philips Healthcare, “Wearable Biosensor,” vol. 13, no. 2, pp. 1–10, 2018.
[3] K. Guk et al., “Evolution of wearable devices with real-time disease monitoring for personalized
healthcare,” Nanomaterials, vol. 9, no. 6, pp. 1–23, 2019.
[4] J. Kim, A. S. Campbell, B. E. F. de Ávila, and J. Wang, “Wearable biosensors for healthcare
monitoring,” Nat. Biotechnol., vol. 37, no. 4, pp. 389–406, 2019.
[5] R. K. Pandey, “Wearable Biosensors,” vol. 2016, no. 17, pp. 1–15, 2008.
[6] W. Gao et al., “Wearable sweat biosensors,” Tech. Dig. - Int. Electron Devices Meet. IEDM,pp.
6.6.1-6.6.4, 2017.
[7] Handbook of biomedical instrumentation ,Khandpur ,pp-138,233,238
[8] https://en.wikipedia.org/wiki/Biosensor
[9] H. H. Asada, P. Shaltis, A. Reisner, S. Rhee, and R. C. Hutchinson, “Mobile Monitoring with
Wearable Photoplethysmographic Biosensors,” IEEE Eng. Med. Biol. Mag.,vol. 22, no. 3, pp. 28–
40, 2003.
[10]S. Patel, H. Park,P. Bonato,L. Chan, and M. Rodgers, “A review of wearable sensors and systems
with application in rehabilitation,” J. Neuroeng. Rehabil., vol. 9, no. 1, p. 21, 2012.

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Wearable Biosensor Seminar Report

  • 1. 1 | P a g e WEARABLE BIO SENSOR Seminar Report Submitted in partial fulfilment for the award of degree of Bachelor of Technology In Electronics & Communication Engineering Submitted by: Guided by: Department of Electronics Engineering Rajasthan Technical University, Kota May 2020 NAME: - PRITAM CRN:- 16/373 Dr. Deepak Bhatia Associate Professor
  • 2. 2 | P a g e CERTIFICATE This is to certify that Seminar Report entitled “WEARABLE BIO SENSOR” which is submitted by PRITAM in partial fulfillment of the requirement for the award of degree B. Tech. in Department of Electronics & Communication, RAJASTHAN TECHNICAL UNIVERSITY, KOTA is a record of the candidate own work carried out by her under my supervision. The matter embodied in this thesis is original and has not been submitted for the award of any other degree. Date: Supervisor
  • 3. 3 | P a g e DECLARATION I hereby declare that this submission is my own work and that, to the best of my knowledge and belief, it contains no material previously published or written by another person nor material which to a substantial extent has been accepted for the award of any other degree or diploma of the university or other institute of higher learning, except where due acknowledgment has been made in the text. Signature: Name – PRITAM Roll No. –16EUCEC036
  • 4. 4 | P a g e ACKNOWLEDGEMENT It gives us a great sense of pleasure to present the report of the B. Tech seminar undertaken during B. Tech. Final Year. I owe special debt of gratitude to Dr. DEEPAK BHATIA , Department of Electronics & Communication, RAJASTHAN TECHNICAL UNIVERSITY,KOTA for his constant support and guidance throughout the course of my work. His sincerity, thoroughness and perseverance have been a constant source of inspiration for me. It is only his cognizant efforts that my endeavors have seen light of the day. I also take the opportunity to acknowledge the contribution of Dr. Dr. Jankiballabh Sharma, Department of Electronics & Communication, RAJASTHAN TECHNICAL UNIVERSITY, KOTA, for his full support and assistance. I also would not like to miss the opportunity to acknowledge the contribution of all faculty members of the department for their kind assistance and cooperation during the development of my project. Last but not the least, i acknowledge my friends for their contribution in the completion of the project. Signature: Name : PRITAM Roll No.:16EUCEC036 Date : 03-05-2020
  • 5. 5 | P a g e INDEX S.R.NO. TABLE OF CONTENT PAGE NO I. COVER PAGE 01 II. CERTIFICATE 02 III. DECLARATION 03 IV. ACKNOWLEADGEMENT 04 V. INDEX 05 VI. TABLE OF FIGURE 06 VII. ABSTRACT 07 1. INTRODUCTION 08 2. - CLASSFICATION OF WEARABLE BIOSENSOR 12 2.1 RING SENSOR 12 2.2 SMART SHIRT (WEARABLE MOTHERBOARD) 17 2.3 WEARABLE SWEAT BIO SENSOR 26 2.4 TATTO SENSOR 34 2.5 CONATCT LENS SENSOR 36 2.6 THICK FILM TEXTILE SENSOR 37 2.7 MOUTH GUARD BIO SENSOR 38 2.8 WRIST WATCH 39 2.9 WRIST/HAND BAND SENSOR 40 2.10 GFC GLUCOSE SENSOR 41 2.11 PACKAGE LATCATE CHIP SENSOR 42 3. CONCLUSION 43 4. FUTURE TRENDS 44 5. REFERANCES 46
  • 6. 6 | P a g e TABLE OF FIGURE FIG.NO. TABLE OF FIGURE PAGE NO 1 Systematic representation of function of bio sensor 8 2 Health monitoring system based on wearable bio sensor 10 3 Noise cancellation mechanism 13 4 Prototype of Ring Sensor 13 5 Block diagram of Ring Sensor 14 6 Smart shirt 17 7 Requirements of Smart Shirts 18 8 Architecture of Smart Shirt 20 9 Applications of Smart Shirt 23 10 Wearable sweat biosensors which continuously measure a variety of sweat compositions for Health monitoring. 26 11 Sweat bio sensing platforms 27 12 The categories of wearable chemical sensors. 28 13 Fully integrated sensor arrays (FISA) for multiplexed perspiration analysis 28 14 System level characterizations and compensation 29 15 On-body real-time multiplexed monitoring 30 16 Wearable sensors for Ca2+ and ph monitoring of body fluids 31 17 Flexible micro sensor arrays for multiplexed heavy metals analysis. 32 18 Transdermal alcohol sensor 32 19 One-day monitoring of sweat glucose concentrations using wearable diabetes patch and Blood glucose levels using commercial blood glucose meter 33 20 Hydration status analysis during group outdoor running using the wearable sensors. 33 21 Tattoo-based transdermal alcohol sensor 34 22 Schematic procedure to fabricate tattoo seal biosensor. 35 23 A schematic of the contact lens sensor 36 24 Screen –printed carbon electrodes on the underwear 37 25 Mouth guard biosensor with fully integrated wireless instrumentation electronics to Continuous and real time electrochemical monitoring. Adapted 38 26 Mouth guard biosensor for lactate monitoring. 38 27 Glucowatch for continuous glucose monitoring 39 28 Wrist and head band biosensors 40 29 Working principle of GCF biosensor for glucose monitoring with calibration curves 41 30 Packaged lactate chip sensor 42
  • 7. 7 | P a g e ABSTRACT Recent advancements in miniature devices have fostered a dramatic growth of interest of wearable technology. Wearable Bio-Sensors (WBS) will permit continuous cardiovascular (CV) monitoring in a number of novel settings. WBS could play an important role in the wireless surveillance of people during hazardous operations (military, firefighting, etc.)or such sensorscould be dispensed during a masscivilian casualty occurrence. They typically rely on wireless, miniature sensors enclosed in ring or a shirt. They take advantage of handheld units to temporarily store physiological data and then periodically upload that data to a database server via wireless LAN or a cradle that allow Internet connection and used for clinical diagnosis.
  • 8. 8 | P a g e Chapter:1 INTRODUCTION Wearable sensors and systems have evolved to the point that they can be considered ready for clinical application. The use of wearable monitoring devices that allow continuous or intermittent monitoring of physiological signals is critical for the advancement of both the diagnosis as well as treatment of diseases. Wearable biosensors offer an endless range of potential ways to provide terms of timely diagnoses and to monitor the efficacyof treatments.Being able to trackpersonal health metrics, measuring and maintaining patients’ drug levels with great accuracy,maintain accurate measurements, as well as monitor potential threats in patients’ external environments are a few of the many benefits of wearable biosensors. Measuring, maintaining are just a few of the m a n y uses biosensors have, some of these applications, particularly those intended for the sports industry, are likely to be available in medium term, which is about three to five yearswhile, and will be made available long-term, which is above five year A biosensor is a machine that consists of a bio receptor and a transducer and is used for transforming a biological response into an electrical signal. The biosensor machine empowers one to measure the target analytic by not using the reagents and also to decide the concentration of substances,this machine is also used in the monitoring of the glucose in diabetes patients, detects the pesticides and also the contaminants of the river water,it also detects the poisonous metabolites. The continuous measurement of raw materials and products plays a vital role in the control of a biochemical process. Wearable systems are totally non-obtrusive devices that allow physicians to overcome the limitations of ambulatory technology and provide a response to the need for monitoring individuals over weeks or months. They typically rely on wireless miniature sensors enclosed in patches or bandages or in items that can be worn, such as ring or shirt. The data sets recorded using these systems are then processed to detect events predictive of possible worsening of the patient’s clinical situations or they are explored to access the impact of clinical interventions. Biosensors are chemical sensors in which the analyte recognition is sensed through biochemical or biological mechanisms. The interactions between the analyte and the sensing elements determine the biological responses. In these interactions, some physical and chemical properties of the sensing elements may vary depending on the analyte concentration. To assess these property changes,the sensor convert the interaction responses into measurable physical quantities. This process of analyte recognition can then be
  • 9. 9 | P a g e achieved through various methods, such asrecognition by ions, nucleic acids, enzymes,and/or by cells and tissues. Specifically, bio receptors are highly selective towards the analyte. Fig. 1 Systematic representation of function of bio sensor According to Transparency Market Research,the market potential for wearable biosensors is high, and projected to reach a market value of $21.6 billion by 2020. It is projected that “The biosensors market is expected to witness considerable growth owing to its wide array of applications in diabetes monitoring, cardiac monitoring, drug discovery, agriculture, environmental and bio-defense practices”. The growth of this market has been aided by the rise in the diabetic population coupled with an increase in the increased demand for home-care and point-of-care diagnostics. Innovation reduced not only the size of biosensors but reduced the pain experienced by the user as well. Primarily, the method of collecting input from the user was to prick the user to obtain a droplet of blood. To eliminate the pain of a prick but still be able to collect data, researchers came to the solution to use different media for analysis such as Interstitial Fluid (ISF), sweat, tears, saliva, and many other types of media. The use of wearable biosensors is always beneficial as they provide continuous monitoring. They are easy to use and their use reduces the hospitalization fee. Wearable biosensors are not only responsible for the measurement of a biomarker, but also sends the signals through the advanced wireless systems to the control unit. Emergency situations are detected via data processing implemented throughout the system and an alarm message is sent to an emergencyservice center to provide immediate assistance to patients. This creates a two-way feedback between doctors and patients allowing patients to get advice from their doctors without physically going to the hospital. Utilizing the information provided by wearable biosensors, patients have the potential to shorten hospital staysand reduce readmissions by being informed about their health. A conceptual representation of a system for remote monitoring is shown in Fig 2.
  • 10. 10 | P a g e Fig. 2 Health monitoring system based on wearable bio sensor 1.1History of Wearable Biosensors: In the year of 1956, Professor Lenald C Clack proclaimed a paper about oxygen electrode and later in the year of 1962, the Professor came with an advanced idea that includes the enzyme transducers as the membrane enclosed sandwiches. After this many people did many developments in it and then in the year of 1976, La Roche introduced the Lactate Analyzer LA640. In 1987, for home blood glucose monitoring a pen sized meter was launched and then in the year of 1996, the sales of this meter reached 175 million dollars. 1.2Applications of the Wearable Biosensors: The applications of the wearable biosensors are as follows:  The biosensors are used in medical care for both the clinical purpose and the laboratory purpose.  The biosensors are used in the resolution of food quality.  It is used in detecting the pollutants of an environment.  The biosensors are used in the industrial process control.  In the process control, it will be able to measure the materials in the process flow of temperature, acidity regulations and the pressure.  The advancement of the biosensors in the industries can develop the manufacturing mechanisms.  It plays a vital role in the production of pharmaceuticals.  The biosensors are also used in the replacement of organs like an artificial pancreas for the diabetic patient.
  • 11. 11 | P a g e 1.3Needfor Biosensors: The need for the biosensors is in the following areas:  In the diagnostic market  In the clinical testing  In other materials that include veterinary and agricultural applications  In specificity, it is used to measure particular analytes  In the speed  Simplicity and continuous monitoring capability
  • 12. 12 | P a g e Chapter:2 CLASSIFICATION OF WEARABLE BIO SENSOR 2.1 RING SENSOR It is a pulse oximetry sensor that allows one to continuously monitor heart rate and oxygen saturation in a totally unobtrusive way. The device is shaped like a ring and thus it can be worn for long periods of time without any discomfort to the subject. The ring sensor is equipped with a low power transceiver that accomplishes bi-directional communication with a base station, and to upload date at any point in time. 2.1.1 BASIC PRINCIPLE OF RING SENSOR:- Each time the heart muscle contracts, blood is ejected from the ventricles and a pulse of pressure is transmitted through the circulatory system. This pressure pulse when traveling through the vessels, causes vessel wall displacement which is measurable at various points.inorder to detectpulsatile blood volume changesby photoelectric method, photo conductors are used. Normally photo resistors are used, for amplification purpose photo transistors are used. Light is emitted by LED and transmitted through the artery and the resistance of photo resistor is determined by the amount of light reaching it.with each contraction of heart, blood is forced to the extremities and the amount of blood in the finger increases.it alters the optical density with the result that the light transmission through the finger reduces and the resistance of the photo resistor increases accordingly. The photoresist or is connected as a part of voltage divider circuit and produces a voltage that varies with the amount of blood in the finger. This voltage that closely follows the pressure pulse 2.1.2 WORKING The LEDs and PD are placed on the flanks of the finger either reflective or transmittal type can be used. For avoiding motion disturbances quite stable transmittal method is used. Transmittal type has a powerful LED for transmitting light across the finger. This power consumption problem can be solved with a light modulation technique using high-speed devices. Instead of lighting the skiing continuously, the LED is turned ON only for a short time, say 10-100 ns, and the signal is sampled
  • 13. 13 | P a g e within this period, high frequency, low duty rate modulation is used for preventing skin-burning problem. The motion of the finger can be measure with an optical sensor. This motion detector can be used not only for monitoring the presence of motion but also for cancelling the noise. By using PD-B as a noise reference,a noise cancellation filter can be built to eliminate the noise of PD-A which completes with the noise references used. And adaptive noise cancellation method is used. Fig. 3 Noise Cancellation Mechanism The noise-canceling filter combines two sensor signals; one is the main signal captured by PD-A and the other is the noise reference obtained by PD-B. The main signal mostly consists of the truce pulsate signal, but it does contain some noise. If we know the proportion of noise contained in the main signal, we can sensate the contained in the main signal, we can generate the noise of the same magnitude by attending the noise reference signaland then subtract the noise from the main signal to recover the true pulsatile signal. Fig. 4 Prototype of Ring Sensor
  • 14. 14 | P a g e The ring has a microcomputer performing all the device controls and low level signal processing including LED modulation, data acquisition, filtering, and bi-directional RF communication. The acquired waveformssampled at100Hz are transmitted to a cellular phone carriedby the patient through an RF link of 105Kbps at a carrier frequency of 915 MHz The cellular phone accesses a website for data storage and clinical diagnosis. 2.1.3 BLOCK DIAGRAM OF RING SENSOR Fig. 5 Block diagram of Ring Sensor Power for light source, photo detector, RF transmitter and analog and digital processing units provided by a tiny cell battery used for wrist watches. Lifetime is 2 or 3 weeks.
  • 15. 15 | P a g e Light Source: - Light source for the ring sensor is the LED, approximately wavelength of 660 nm. Photo Detector: - Photo detector is normally photodiode or phototransistor used for detecting the signal from the LED. RF Transmitter: - It is used for transmitting the measured signals. Its carrier frequency is 915MHz. LED Modulation Power consumption problem can be solved with a lighting modulation technique. Instead of lighting the skin continually the LED is turned on only for a short time, say 100-1000ns and the signal is sampled within the period. High frequency low duty cycle modulation implemented minimizes LED power consumption. Data Acquisition:-It is used to collect the data from sensor and data are sampled and recorded. Filtering The signal from the PD-Basa noise reference a noise cancellation filter canbe built to eliminate the noise of PD-Awhich correlateswith the noise reference signal. For noise cancellation we use the adaptive noise filter.
  • 16. 16 | P a g e 2.1.4 APPLICATION OF THE RING SENSOR  CATRASTOPHE DETECTION  Wireless supervision of people during hazardous operations Ex: military, fire fighting  In an overcrowded emergency department  CHRONIC MEDICAL CONDITION  in cardiovascular disease for monitoring the hyper tension  chronic surveillance of abnormal heart failure 2.1.5 ADVANTAGE  continuous monitoring  detection of transient phenomena  promote further diagnostic and therapeutic measures  easy to use  reducing hospitalization fee 2.1.6 DISADVANTAGE  initial cost is high  limited number of physiological parameters are to be monitored
  • 17. 17 | P a g e 2.2 SMART SHIRT (WEARABLE MOTHERBOARD) Smart shirt developed at Georgia tech which represents the first attempt at relying an unobtrusive, mobile and easy to use vital signs monitoring system; presents the key applications of the smart shirt technology along with its impact on the practice of medicine; and covers key opportunities to create the next generation of truly “adaptive and responsive” medical systems. Research on the design and development of a smart shirt fort a combat casualty care has led to the realization of the world’s first wearable motherboard or an “intelligent” garment for the 21st century. The Georgia tech wearable motherboard (GTWM) uses optical fibers to detect bullet wounds and special sensors and interconnects to monitor the body vital signs during combat conditions. This GTWM (smart shirt) provides an extremely versatile framework for the incorporation of sensing, monitoring and information processing devices. The principal advantage of smart shirt is that it provides for the first time a very systematic way of monitoring the vital signs of humans in an unobtrusive manner Fig. 6 SMART SHIRT 2.2.1REQUIREMENTS OF SMART SHIRT Casualties are associated with combat and sometimes are inevitable. Since medical resources are limited in a combat scenario, there is critical need to make optimum use of the available resources to minimize the loss of human life, which has value that is priceless. In a significant departure from the past, the loss of even a single soldier in a war can alter the nation’s engagement strategy making it all the important to save lives. Similarly on the civilian side, the population is aging and the cost of the health care delivery is expected to increase at a rate faster than it is today. With the decreasing number of doctors in rural areas,the doctor/patient ratio is in certain instances reaching unacceptable levels for ensuring a basic sense of security when they leave the hospital because they feel “cutoff” from the continuous watch and care they received in the hospital. This degree of uncertainty can greatly influence their
  • 18. 18 | P a g e postoperative recovery.Therefore there is a need to continuously monitor such patients and give them the added peace of mind so that the positive psychological impact will speed up the recovery process. Mentally ill patients need to be monitored on a regular basis to gain a better understanding of the relationship between their vital signs and their behavioral patterns so that their treatments can be suitably modified. Such medical monitoring of individuals is critical for the successful practice of telemedicine that is becoming economically viable in the context of advancements in computing and telecommunication, likewise continuous monitoring of astronautsin space,of athletes during practice sessions and in competition, of law enforcement personnel and combat soldiers in the line of duty are all extremely important. Fig. 7 Requirements of Smart Shirts
  • 19. 19 | P a g e 2.2.2ARCHITECTURE The GTWM was woven into a single –piece garment (an undershirt) on a weaving machine to fit a 38-40” chest. The plastic optical fiber (POF) is spirally integrated into the structure during the fabric production process without any discontinuities at the armhole or the segms using a novel modification in the weaving process. An interconnection technology was developed to transmit information from (and to) sensors mounted at any location on the body thus creating a flexible “bus” structure. T-connectors –similar to “button clips” used in clothing are attached to the fibers that serve as a data bus to carry the information from the sensors (eg: ECG sensors) on the body. The sensorswill plug into these connectors and atthe other end similar T-connector will be used to transmit their information for monitoring equipment or DARPS (Defense Advanced Research Projects Agency) personnel status monitor .By making the sensors detachable from the garments, the versatility Iof the Georgia Tech Smart Shirt has been significantly enhanced. Since shapes and sizes of humans will be different, sensors can be positioned on the right locations for all users and without any constraints being imposed by the smart shirt can be truly “customized”. Moreover the smart shirt can be laundered without any damage to the sensors themselves. The interconnection technology hasbeen used to integrate sensorsfor monitoring the following vital signs: temperature, heart rate and respiration rate .In addition a microphone has been attached to transmit the weaver’s voice data to monitoring locations. Other sensors can be easily integrated into the structure. The flexible data bus integrated into the stricture transmits the information from the suite of the sensors to the multifunction processor known as the Smart shirt controller. This controller in turn processes the signals and transmit them wirelessly to desired locations (eg: doctor’s office, hospital, and battlefield). The bus also serves to transmit information to the sensors (and hence the weaver) from the external sources, thus making the smart shirt a valuable information infrastructure. A combat soldier sensor to his body, pulls the smart shirt on, and attaches the sensors to the smart shirt. The smart shirt functions like a mo0therboard, with plastic optical fibers and other special fibers woven throughout the actual fabric of the shirt. To pinpoint the exact location of a bullet penetration, a “signal” is sent from one end of the plastic optical fiber to a receiver at the other end. The emitter and the receiver are connected to a Personal Status Monitor (psm) worn at the hip level by the soldier. If the light from the emitter does not reach the receiver inside the PSM,it signifies that the smart shirt has been penetrated (i.e.; the soldier has been shot). The signal bounces back to the PSM forum the point of penetration, helping the medical personnel pinpoint the exact location the solider wounds.
  • 20. 20 | P a g e The soldiers vital signs –heart rate, temperature, respiration rate etc. are monitored in two ways: through the sensors integrated into the T-shirt: and through the sensors on the soldier’s body, both of which are connected to the PSM. Information on the soldiers wound and the condition is immediately transmitted electronically from the PSM to a medical triage unit somewhere near the battlefield. The triage unit them dispatches the approximate medical personnel to the scene .The Georgia tech smart shirt can help a physician determine the extent of a soldiers injuries based on the strength of his heart beat and respiratory rate. This information is vital for accessing who needs assistance first during the so-called “Golden Hour” in which there are numerous casualties. Fig. 8 Architecture of Smart Shirt
  • 21. 21 | P a g e 2.2.3APPLICATIONS OF SMART SHIRT  Combat casualty care.  Medical monitoring.  Sports/ Performance monitoring.  Space experiments.  Mission critical/ hazardous application.  Fire- fighting.  Wearable mobile information infrastructure. The vital signs information gathered by the various sensors on the body travels through the smart shirt controller for processing, from these, the computed vital signals are wirelessly transmitted using the “communication information infrastructure” in place in that application (e.g.: the firefighters, communication systems, battlefield communication infrastructure, the hospital network) to the monitoring station. There, the back-end Data display and Management system – with a built –in knowledge –based decision support system- in reverse these vital signs ask in real-time and provide the right response to the situation. Table 1 summarizes the broad range of application of the smart shirt technology. The table also shows the application type and the target population that can utilize the technology.
  • 22. 22 | P a g e Table No:- 1 Wearable smart shirt applications
  • 23. 23 | P a g e Fig. 9 Applications of Smart Shirt
  • 24. 24 | P a g e 2.2.4IMPACT OF THE SMART SHIRT The smart shirt will have significant impact on the practice of medium since it fulfills the critical need for a technology that canenhance the quality of life while reducing the health care costacross the continuum of life that is from newborns to senior citizens, and acrossthe continuum of medical care that is from hospitals and everywhere in between. The smart shirt can contribute to reduction in health care cost while enhancing the quality of life. For instance, patients could wearthe smart shirt at home and be monitored by a monitoring station; thereby avoiding hospital stay cost and reducing the overall cost of healthcare. At also same home, a home setting can contribute to faster recovery. For example, if the patient recovering at home from heart surgery is wearing the smart shirt, the ECG can be transmitted wirelessly (through mobile phone, internet etc.) to the hospital on a regular basis. This monitoring will help the patient feelmore “secure” and will facilitate the recuperation while simultaneously reducing the cost time associated with recovery. Moreover, in the event of an emergency, the doctor can be notified instantaneously. Using the online medical records (available over the web) the physician can administrate the right investment at the right time at the right cost and indeed save a life, thereby realizing the full potential of the smart shirt technology. Furthermore, persons who have known disorders can wear the smart shirt and be under constant monitoring of the physical conditions by medical personnel. Yet another potential impact of the smart shirt technology is the eventual disappearance of geographical/physical boundaries as barriers for individual seeking the best in healthcare worldwide. The smart shirt technology has the means to provide unobstructed monitoring for individuals and can thereby play a critical role disease management for the large numbers of individuals at risk for high blood pressure, heart disease, diabetes, chronic bronchitis, and depression by enabling early systematic intervention.
  • 25. 25 | P a g e 2.2.5ADVANTAGES OF THE SMART SHIRT  Continuous monitoring  Right Treatment at the right time at the right cost  Easy to wear and takeoff.  Reducing the health care cost 2.2.6DISADVANTAGES OF THE SMART SHIRT  Initial cost is high  Battery life is less
  • 26. 26 | P a g e 2.3WEARABLE SWEAT BIO SENSOR:- Wearable biosensors are expected to play a significant role in future healthcare as they allow real-time and non-invasive (or minimally invasive) monitoring of an individual’s health state. Currently commercialized wearable sensors are only capable of tracking an individual’s physical activities and vital signs but fail to provide insightful physiological information at the molecular level. Human sweat,an important body fluid that can be retrieved conveniently and non-invasively, contains rich information about our health and fitness conditions. Therefore,sweatcanbe an ideal candidate for developing wearable chemical biosensors which may provide insightful physiological information. In the past decade,tremendous progress has been made on developing such sweat biosensors as illustrated in Table No-2 These wearable biosensors have been used to measure the detailed sweat profiles of a wide spectrum of analytes including metabolites, electrolytes and heavy metals during various indoor and outdoor physical activities. Fig. 10 Wearable sweat biosensors which continuously measure a variety ofsweat compositions for health monitoring. Platform Analytes Refs. Temporary tattoo Lactate, pH, NH4 + , Na+ , Zn2+ , ethanol 7-12 pH 13 Patch Glucose, lactate, Na+ , K+ , pH, Ca2+ , Zn2+ , Cu2+ 4-6 Glucose, pH 14 Na+ 15-17 Cl- 18, 19 pH 20, 21 Table No:- 2 Summary of the wearable sweat biosensor .
  • 27. 27 | P a g e 2.3.1 SYSTEM DESIGN OF WEARABLE BIO SENSOR:- 2.3.1.1 Platform of sweat biosensor:- Wearable sweat biosensor are usually prepared on a flexible substrate that forms conformal contact with the skin, while minimizing the required sweat volume to perform proper sweat collection and analysis. Different sensing platforms have been developed in the past decade which include the epidermal tattoos, flexible patches/bands and textiles. Fig. 11 Sweat bio sensing platforms: a) epidermal temporary tattoo b) adhesive RFIDsensor patch c) flexible and stretchable sensor patch d) fully integrated flexible sensor band. 2.3.1.2 Target of analytes Avariety of sweatbiomarkers are closely relatedto human health conditions, andthey canserve asexcellent targeting analytes for wearable sweat biosensors. For example, sweat chloride test is the gold standard for diagnosis of cystic fibrosis; excessive loss of Na+ and K+ in sweat could result in hyponatremia, hypokalemia, muscle cramps or dehydration; sweat ethanol and glucose are reported to be metabolically related to blood ethanol and glucose; sweat lactate can potentially serve as a sensitive marker of pressure ischemia. Monitoring these important biomarkers using wearable sweat biosensors can offer us insightful physiological and clinical information. 2.3.1.3 Detection techniques:- Based on detection strategies, current wearable sweat biosensors include optical sensors for sweat rate and sweat pH analysis , impedance-based sensors for sweat conductivity and sweat rate monitoring, ion selective electrodes for electrolyte sensing (such as Na+ ,K+ , H+ , NH4 + ,Ca2+ , Cl- ), enzymatic amperometric sensors for metabolite sensing (such as glucose, lactate,uric acid, ethanol), and stripping based sensors for heavy metal analysis (such as Cu, Zn, Pb, Cd, Hg).
  • 28. 28 | P a g e Fig. 12 The categories of wearable chemical sensors. 2.3.1.4 System integration Since sweat secretion is complex, to extract more useful information, simultaneous detection of multiple sweatbiomarkers through system integration is critical. A fully integrated multiplexed sweat sensing system has been developed by merging plastic-based sensors that interface with the skin and silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. Figure 13 shows a schematic of the sweat sensor array consisting of 2 metabolite sensors (glucose and lactate), 2 electrolyte sensors (Na+ and K+ ) and a skin temperature sensor. Figure 13 illustrates the system-level overview of the signal transduction, processing, and wireless transmission paths to facilitate multiplexed on body measurements. Eventually the data from the system is wirelessly transmitted to a cellphone and displayed in a custom developed application. Fig. 13 Fully integrated sensor arrays (FISA) for multiplexed perspiration analysis a) Schematic of the sensor array (including glucose, lactate, sodium, potassium and temperature sensors). b) System-level block diagram of the FISA.
  • 29. 29 | P a g e 2.3.1.5 System level characterizations and compensation:- It has been shown that each sensor can maintain excellent selectivity upon varying concentrations of each analyte during system-level multiplexed measurements (Figure 14a). However, temperature and pH have shown great influence on the performance of amperometric enzymatic based sensors (Figure14b and 14c). Utilization of such fully integrated wearable device can facilitate measurement accuracy through real-time calibration and signal compensation. Fig. 14 . a) System-levelmultiplexedmeasurements andinterference studies. b)System-levelreal- time temperature andpH (c) compensation for enzymatic sensors. 2.3.2 Real time on body sweat analysis for health monitoring The sweat biosensors can be worn on body for real-time perspiration analysis during a variety of physical activities, allowing non-invasive health monitoring. Recently, the on body evaluation of sweat biosensors has opened the door for a wide range of physiological and clinical investigations. 2.3.2.1 Real time analysis of major sweat metabolites (glucose and lactate) and major electrolytes (Na+ and K+) Physiological monitoring of sweat lactate and sodium using wearable sweat sensors has been demonstrated on different platforms. Simultaneous measurements of multiple sweat analytes using a fully-integrated sensing system wasalso reported during a cycling. Figure 15 shows that, asperspiration begins, both lactate and glucose levels in sweat decrease gradually. The decreased sweat lactate and glucose levels is owing to the dilution effect caused by an increase in sweat rate, which is visually observed as exercise continues.
  • 30. 30 | P a g e Sweat [Na+ ] increases and [K+ ] decreases in the beginning of perspiration, in line with the previous ex-situ studies from the collected sweat samples. Both [Na+ ] and [K+ ] stabilize as cycling continues. Fig. 15 On-body real-time multiplexed monitoring ofsweat glucose, lactate, sodium, potassium as well as the skin temperature using a FISA worn on a subject’s forehead during a constant-load cycling exercise 2.3.2.2 . Real time sweat Ca2+ and pH monitoring Calcium is an essentialcomponent for human metabolism, and pH is crucial for potential disease diagnosis. Sweat pH sensors have been measured optically and electrochemically. A fully integrated wearable sensing device (Figure 16a) has also been demonstrated for simultaneous evaluation of pH and Ca2+ in human perspiration which is particularly important considering that free Ca2+ level in bio fluids is dependent on pH . Figure 16 b displays the sweat profiles of a subject during a constant load cycling exercise: sweat pH increases gradually for 5 min and then stabilizes in the remaining cycling exercise while the Ca2+ sensor shows an opposite trend. The responses of these sensors were validated with a commercial pH meter and inductively coupled plasma-mass spectrometry.
  • 31. 31 | P a g e Fig. 16 Wearable sensors for Ca2+ and pH monitoring of body fluids a) A schematic of a flexible sensor array. b) On-body Ca2+ and pH analysis during a constant-load cycling exercise 2.3.2.3 Sweat heavy metal monitoring:- Besides metabolites and electrolytes, a variety of heavy metals canbe found in human sweatand are closely related to human health conditions. Printed tattoo based sweat sensors have been used for sweat Zn monitoring. Recently, a micro sensor array containing biocompatible gold and bismuth electrodes has been developed to simultaneously measure multiple heavy metals in sweat including Zn, Cd, Pb, Cu, and Hg through stripping voltammetry (Figure 17a-c). Sweat Cu and Zn were monitored on-body during a cycling exercise (Figure17d). These trace metals sensors can monitor heavy metal exposure and aid in related clinical investigations.
  • 32. 32 | P a g e Fig. 17 Flexible micro sensor arrays for multiplexed heavy metals analysis. a) Schematic of microelectrodes. b, c) Characterization of Au and Bi microelectrodesfor trace metal detection. d) On body trace metal detection during a constant-load cycling exercise. 2.3.2.4 Ethanol monitoring:- High blood alcohol levels can cause severe traffic accidents and increased risks for cancers while sweat ethanol is reported to be the same as blood alcohol concentration (BAC). Wearable sweat ethanol sensors which integrate an iontophoresis based sweat extraction system along with a flexible wireless circuit board have been developed. These sensors demonstrate clear differences in the current response before and after alcohol consumption, reflecting the increase of blood ethanol levels (Figure 18). Fig. 18 Transdermal alcohol sensor . a) Schematic diagram of the wireless operation of the iontophoretic - sensing tattoo device for transdermal alcohol sensing. b) Experiments to demonstrate correlation between BAC level and current response from the tattoo biosensor measured.
  • 33. 33 | P a g e 2.3.2.5 Glucose correlation study:- The wearable sweat biosensors can potentially be used for diabetes monitoring and control. A graphene- based electrochemical device has recently been developed to measure real-time sweat glucose through pH calibration. With the aid of this device, a correlation betweensweatglucose data from the wearable diabetes patch and those from a commercial glucose assay as wellas blood glucose data from a commercial glucose meter was observed.fig-19) Fig. 19 One-day monitoring ofsweat glucose concentrations using wearable diabetes patch and blood glucose levels using commercial blood glucose meter 2.3.2.6 Dehydration monitoring:- Monitoring hydration status is of the utmost importance to athletes because fluid deficit impairs endurance performance. The sweat biosensors can be potentially used for effective and non-invasive monitoring of the electrolyte loss (Figure 20a) Figure 20b shows that sweat [Na+ ] measured from an integrated sensor array was stable throughout running in dehydration trials (with regular water intake). On the other hand, a substantial increase in sweat [Na+ ] was observed in dehydration trials (without water intake) after 80 min when subjects had lost a large amount of water (Figure 20c). The results show that through sweat composition analysis, insightful information may be provided for athletic performance applications. Fig. 20 Hydration status analysis during group outdoor running using the wearable sensors. a) Schematic illustration showing the group outdoor running trial based on wearable FISAs (packaged as ‘smart headbands’). The data are real-time transmittedto the user’s cellphone anduploadedto cloud servers. b) Representative real-time sweat sodium levels during an endurance run with water intake (b) and an endurance run without water intake (c).
  • 34. 34 | P a g e 2.4 Tattoo sensor:- Tattoo sensors are separated into two categories based upon the lifetime of the sensor: temporary and long term. Temporary tattoo sensors are designed as disposable sensors with a maximum life time of 2-3 days. Long term tattoo sensors are designed to uphold their functionality for an extended period. Here in depth we will discuss under those categorize; temporary tattoos sensor, smart tattoos sensor. 2.4.1 Temporary tattoo sensor:- Wearable temporary tattoos is capable of monitoring alcohol in a real-time and noninvasive way via the integration of printed and flexible iontophoretic-sensing electrodes with wireless electronics. The flexible tattoo-based iontophoretic alcohol monitoring patch uses transdermal delivery of a drug, pilocarpine to induce sweat via constant-current iontophoresis. Followed by amperometric bio sensing of the sweat’s ethanol (Fig. 21D). The latter relies on an alcohol-oxidase (AOx) enzymatic patch along with a printed Prussian blue (PB) electrode transducer. A flexible supporting module with electronic readout was also integrated for wireless data transmission (Fig. 21). The electrochemical performance of the alcohol biosensor wasvalidated first in a medium bufferovera wide concentration range of 0–36 mM ethanol, which corresponded to the physiological level of ethanol found in sweat. The enzymatic sensors are selective towards ethanol and have very negligible interference with the co-existing compounds. Fig. 21 Tattoo-based transdermal alcohol sensor. (A) Schematic diagram of an iontophoretic- sensing tattoo device,containing the iontophoretic electrode.
  • 35. 35 | P a g e 2.4.2 Smart tattoo sensor:- The pursuit ofa more accurate blood glucose level reading led to the invention of carbonnanotube (CNT) ‘tattoos’. Most recently glucose sensors involve the injection of the enzyme, GOx which breaks down glucose. These sensors have not meet the desired levelof stability and are only used for seven days of use. What distinguishes smart tattoo sensor is the foundation of their use of its carbon nanotubes base. In addition, these smart tattoo sensors can be immobilized in hydrogels that are highly biocompatible and compatible with microfabrication. The nanotube smart tattoo sensor would change fluorescence properties in response to blood glucose, and this change could be read out using optical interrogation through the skin. This method would eliminate or reduce the need for patients to take blood samples while allowing data to be collected in a more continuous manner. Researchers usedthe nanoparticle inks in a saline solution that could be injected under the skin like an actualtattoo and have found that the potential lifetime of up to six months for those tattoo. Fig. 22 shows the CNT modified hydrogel based smart tattoo sensor. Glucose, lactate, and alcohol were detected using the smart tattoos. Fig. 22 Schematic procedure to fabricate tattoo seal biosensor. B. Schematic of detection mechanism. Each dehydrogenase and diaphoresis are modified with CNT and hydrogel shells include tetrazolium for optical detection of targets.
  • 36. 36 | P a g e 2.5 Contactlens sensors:- In 2015, the Food and Drug Administration (FDA) approved Google’s patent for contact lenses based sensors. These devices may help healthcare professionals to determine the optimal time of day for measuring a patient’s intraocular pressure. Elevated levels of intraocular pressure associated optic nerve indicates damage that is a characteristic of glaucoma. The contact lenses are able to measure glucose and lactate concentrations. The contact lenses are constructed with a tear film which consists of three layers: an outer lipid layer, aqueous layer, and the inner mucin layer. Fig.23 shows the pictures and configurations of the contact lenses sensors. For these types of sensors, shelf life is limited due to the degradation of enzymes that occurs because of high temperatures and exposure to light. The sensors are tested continuously for 24 hours, using 288 measurements. The stability can, however, be increased by encapsulating the enzyme. Jin Zhang from a Chemical and Biochemical Engineering department, University of Western Ontario, developed the technology which uses engineered nanoparticles embedded into hydrogel lenses. The nanoparticles are engineered to react with the glucose molecules contained in tears. When sugar levels changes, a chemical reaction causes the lens to change color, allowing the wearer to adjust their glucose accordingly. Fig. 23 Aschematic ofthe contact lenssensor, showing the electrical circuitry ofthe sensing system. (b) The contact lens sensor prototype. (c) The wireless chip, which is mounted with the sensor, onto an electronic ring, and then embedded into the contact lens
  • 37. 37 | P a g e 2.6Thick Film textile based sensor: The textile based printed carbon electrodes usually have smooth conductor edges with no defects and cracks. The Screen printed carbon electrodes on the underwear and its voltammetry scan has been shown as Fig.24. The favorable electrochemical behavior is maintained under fold in or stretching stress. It is amperometric sensor which measures NADH and H2O2 from the body by using dehydrogenase oxide basedenzyme with partial voltammetry method. This is undergarment biosensor which remains stable upon successive stretching. Direct screen printing underwear based carbon electrode is used for the operation. Future applications would definitely gain the advantages from tailoring the ink composition and printing conditions as per the customer requirements. Fig. 24 Screen –printed carbon electrodes on the underwear along with the morphology of a single electrode and linear scan voltammetry response for increasing NADH concentrations over the 0- 100 uM range.
  • 38. 38 | P a g e 2.7 Mouth guard bio sensor:- A concept of mouth guard metabolite biosensor has been reported by Kim et al. This is an amperometric biosensor with salivary lactate as an analyte. The direct measurement of lactate in saliva would be used as a diagnostic tool for in vitro monitoring as salivary lactate concentration corresponds with the blood lactate concentration. This wearable oral bio-sensory system uses LOx as an enzyme with Prussian –Blue modified electrode as transducer, acting as artificial peroxidase to offer selective detection of the H2O2. With the aim of stabilizing the device, LOx wasimmobilized on the working electrode surface by the method of polymer entrapping. It parades high selectivity, sensitivity and stability, so as to use them in getting information regarding wearer’shealth,performance and stresslevelthrough Bluetooth orwireless network as displayed in Fig.25. Fig. 25 Mouth guard biosensor with fully integrated wireless instrumentation electronics to continuous and real time electrochemical monitoring. Adapted With the intention of analyzing the stability of the sensor, the researchers have taken continuous readings over the interval of 10 minutes for 2 hours and it has been noticed that the sensor displays high stability with small variations of current signal, ranging between 90% and 106% of the actual response. The good stability shows the proactive actions of the Poly- orthophenylenediamine–LOx interaction, where it is used to stabilize the device. The continuous monitoring responses are known in the Fig.26 below: Fig. 26 Mouth guard biosensor for lactate monitoring.
  • 39. 39 | P a g e 2.8 Wrist watch (gluco watch ) GlucoWatch or GlucoWatch biographer is a wrist watch potentiostat [Fig. 27]. It has GOx enzyme and uses ISF to measure glucose level. This Amperometric sensor works on reverse Iontophoresis phenomenon. The readings have been taken continuously for 12-13 hours with the frequency of 3 per hour. This sensor facilitates with the memory to save up to 4000 readings. It gives 78 readings per wear. After that, one has to change the sensor or stabilize the enzyme in order to continue the use. Gluco watch G2 biographer is suitable for adults and gained FDA approval for use in children and adolescents to monitor glucose continuously. Patients who are insulin dependent are required to monitor their blood glucose levels to ensure that appropriate levels of insulin are circulating. Fig. 27 GlucoWatch for continuous glucose monitoring
  • 40. 40 | P a g e 2.9 Wrist/hand band bio sensor:- A mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). These kinds of biosensors are majorly found in athlete’s group for continuous health monitoring while exercising [Fig.28]. The device come in the form of Wrist or head band with a credit card sized amperometric biosensor embedded in it. It uses GOx and LOx enzyme which monitors glucose contents present in the sweat. Fig. 28 Wrist and head band biosensors
  • 41. 41 | P a g e 2.10 GFC GLUCOSE SENSOR :- To monitor blood glucose level, one method has been used where to realize a non-invasive blood glucose monitor, the Gingival Crevicular Fluid (GCF) wasmeasured.The device to collect GCF wasdeveloped that was designed to be disposal, biocompatible and small enough to be inserted in the gingival crevice for collection of micro liters sample of GCF. Fig. 29 shows working principle of GCF biosensor device and its calibration curves for Capillary Blood Glucose (CBG) and GCF . It senses glucose with the help of GOx enzyme. They monitored continuous responses with increased sensitivity, accuracy, repeatability and specificity. The electrode used is ferrocene modified gold film electrode. Enzyme immobilization was done with cross-linking method. It is a saliva based noninvasive glucose monitoring tool which is widely used for clinical diagnostics. As the repeatability and ultimately stability is higher, it is used in diabetes instantaneous glucose monitoring. Fig. 29 Working principle of GCF biosensor for glucose monitoring with calibration curves
  • 42. 42 | P a g e 2.11 PACKAGED LACTATE CHIP SENSOR:- The electrochemical and biological interferences from saliva were discriminated by using a dual platinum electrode, common Ag/AgClreference electrode and blocking membranes. This is saliva based noninvasive biosensor which monitors lactate level in saliva. It has high operational stability and long term continuous salivary lactate monitoring is possible. The technique of enzyme probe electrode-analyte amperometric monitoring has beenusedin this type of sensor.The structure of packageslactate chip sensors canbe studied through Fig. 30. The reference electrode, counter electrode and cavity of working electrode has been packaged with sealing foil and pores. One of the three salivary glands, sublingual (SL) measurement with Lactate Oxide enzymatic detection has been conducted continuously with high stability. Fig. 30 . Packaged Lactate Chip Sensor
  • 43. 43 | P a g e CHAPTER:3 CONCLUSION The development in wearable biosensors is best example of the integration of biological and engineering sciences. It includes the research of biochemical field and understanding the interaction between biological elements with the target molecule. The use of Nano-transducers has been increased in separation between transducers and bio receptors. The immobilization and stabilization strategies can be selected based on the application. For instance, while developing a sensorwhere durability is not an issue, (e.g.Temporary Tattoo sensors) conventional methods of enzyme stabilization like of enzyme immobilization, cross-linking can be used. For long- term sensing applications immobilization/stabilization using enzyme cloning, sol-gel techniques, hydrogel/Nano gel incorporation would be a viable option. Investigating artificial receptor system that mimic the enzymatic sensing pathway is another viable approach to design biosensor for long- term stability.
  • 44. 44 | P a g e Chapter:4 FUTURE TRENDS Considering future demands of biosensors, researchers are heading towards the best possible solutions to improve the methods of stabilization and achieve the most viable wearable biosensor. In order to maintain the catalytic activity of enzyme in sensors,the sample environment is also a crucial factor to be considered. The previous stabilization strategies have failed because of the diffusion of key reactants and products in and out of the enzyme or matrix surface. For oxidase based enzymes, the coproduced hydrogen peroxide might degrade the enzyme structures. Therefore, to improve the stability of GOx, some new techniques have been proposed which including cross linking, silica sol-gel encapsulation, and molecular cloning. However, these techniques also have some limitations. For examples, sol-gel encapsulation involves production of some harmful organic solvents as byproducts. These are capable of destabilization of encapsulated enzymes. This leads to the decrease in catalytic activity, decrease in substrate specificity and increase enzyme inhibition. The factors which are capable to create an optimum environment for entrapped GOx stability are given by. Molecular cloning is proposed to increase the intrinsic molecular stability [20]. It helps to maintain thermal resistance and pH stability of enzymes. Near future technique to improve the stability is modification of enzymes’ molecular structures. The modification of enzyme structure as per the requirements is most promising and versatile method to gain the stability without affecting performance of biosensors. Another aspect to improve the stability is to incorporate enzymes on a hydrogel or Nano gel matrix. These nanogels creates protecting layers by encapsulating the bio receptors, controls diffusion process and enhances biocompatibility . By providing the “platform” for a suite of sensors that can be utilized to monitor an individual unobtrusively. Smart Shirt technology opens up existing opportunities to develop “adaptive and responsive” systems that can “think” and “act” based on the users condition, stimuli and environment. Thus, the rich vital signs delta steam from the smart shirt can be used to design and experiment “real-time” feedback mechanism (as part of the smart shirt system) to embrace the quality of care for this individual by providing appropriate and timely medical inspections. Certain individuals are susceptible to anaphylaxis reaction (an allergic reaction) when stung by a bee or spider and need a shot of epinephrine (adrenaline) immediately to prevent above illness or even fatalities. By applying advancement in MEMS (Micro-Electromechanical Systems)technology, a feedback system including a dry delivery system-can be integrated into the smart shirt. Of course mechanism to
  • 45. 45 | P a g e guard against inadvertent administration of dry can be built as a part of the control system. Likewise, the Smart shirt’s delta acquisition capabilities can be used to detect the condition when an individual is lapsing into a diabetic shock and this integrated feedback mechanism can provide the appropriate response to prevent a fatality. Thus, the smart shirt represents yet another significant milestone in the endeavor to save and enhance the quality of human life through the use of advanced technologies.
  • 46. 46 | P a g e Chapter:5 REFERENCES [1] A. Sonawane, P. Manickam, and S. Bhansali, “Stability of Enzymatic Biosensors for Wearable Applications,” IEEE Rev. Biomed. Eng., vol. 10, pp. 174–186, 2017. [2] Philips Healthcare, “Wearable Biosensor,” vol. 13, no. 2, pp. 1–10, 2018. [3] K. Guk et al., “Evolution of wearable devices with real-time disease monitoring for personalized healthcare,” Nanomaterials, vol. 9, no. 6, pp. 1–23, 2019. [4] J. Kim, A. S. Campbell, B. E. F. de Ávila, and J. Wang, “Wearable biosensors for healthcare monitoring,” Nat. Biotechnol., vol. 37, no. 4, pp. 389–406, 2019. [5] R. K. Pandey, “Wearable Biosensors,” vol. 2016, no. 17, pp. 1–15, 2008. [6] W. Gao et al., “Wearable sweat biosensors,” Tech. Dig. - Int. Electron Devices Meet. IEDM,pp. 6.6.1-6.6.4, 2017. [7] Handbook of biomedical instrumentation ,Khandpur ,pp-138,233,238 [8] https://en.wikipedia.org/wiki/Biosensor [9] H. H. Asada, P. Shaltis, A. Reisner, S. Rhee, and R. C. Hutchinson, “Mobile Monitoring with Wearable Photoplethysmographic Biosensors,” IEEE Eng. Med. Biol. Mag.,vol. 22, no. 3, pp. 28– 40, 2003. [10]S. Patel, H. Park,P. Bonato,L. Chan, and M. Rodgers, “A review of wearable sensors and systems with application in rehabilitation,” J. Neuroeng. Rehabil., vol. 9, no. 1, p. 21, 2012.